Federer tied Pete Sampras for the most career Wimbledon crowns after dropping the first set but then rebounding for a 4-6, 7-5, 6-3, 6-4 victory over the Scotsman.
The 30-year-old Swiss icon, who made the final after dispatching Novak Djokovic in Friday's semifinals, regained the world No. 1 ranking from the Serb while collecting his 17th career Grand Slam title, the most of any player in history -- but his first since 2010.
"It feels great being back here as the winner ... it's a great moment," he said during the trophy presentation.
Federer reached seven straight Wimbledon finals from 2003-09, winning six of them, and was the 2008 runner-up to Rafael Nadal.
He capped a lengthy rally in the second set with a drop volley, breaking Murray in the 12th game to even the match before rain forced a 40-minute delay at 1-all in the third set.
Centre Court's retractable roof was closed and after play was resumed, the Swiss again broke Murray for a 4-2 lead to cap a marathon game and closed out the set with an ace.
Federer broke for a 3-2 lead in the fourth set with a cross-court backhand past Murray and cruised to the victory -- his 75th career title and his fifth in 2012.
Murray, meanwhile, fell short in his bid to become the first Briton to win a Wimbledon men's title since 1936.
The 25-year-old dropped to 0-4 in Grand Slam finals but broke a streak in which he had failed to win a set.
He also lost to the Swiss in the 2010 Australian Open final -- Federer's most recent Grand Slam title until Sunday -- and in the 2008 U.S. Open finale.